Regulation of Hsp90 ATPase activity by the co-chaperone Cdc37p/p50cdc37

Siligardi, Giuliano, Panaretou, Barry, Meyer, Philippe, Singh, Shradha, Woolfson, Derek N, Piper, Peter W, Pearl, Laurence H and Prodromou, Chrisostomos (2002) Regulation of Hsp90 ATPase activity by the co-chaperone Cdc37p/p50cdc37. Journal of Biological Chemistry, 277 (23). pp. 20151-20159. ISSN 0021-9258

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Abstract

In vivo activation of client proteins by Hsp90 depends on its ATPase-coupled conformational cycle and on interaction with a variety of co-chaperone proteins. For some client proteins the co-chaperone Sti1/Hop/p60 acts as a "scaffold," recruiting Hsp70 and the bound client to Hsp90 early in the cycle and suppressing ATP turnover by Hsp90 during the loading phase. Recruitment of protein kinase clients to the Hsp90 complex appears to involve a specialized co-chaperone, Cdc37p/p50(cdc37), whose binding to Hsp90 is mutually exclusive of Sti1/Hop/p60. We now show that Cdc37p/p50(cdc37), like Sti1/Hop/p60, also suppresses ATP turnover by Hsp90 supporting the idea that client protein loading to Hsp90 requires a "relaxed" ADP-bound conformation. Like Sti1/Hop/p60, Cdc37p/p50(cdc37) binds to Hsp90 as a dimer, and the suppressed ATPase activity of Hsp90 is restored when Cdc37p/p50(cdc37) is displaced by the immunophilin co-chaperone Cpr6/Cyp40. However, unlike Sti1/Hop/p60, which can displace geldanamycin upon binding to Hsp90, Cdc37p/p50(cdc37) forms a stable complex with geldanamycin-bound Hsp90 and may be sequestered in geldanamycin-inhibited Hsp90 complexes in vivo.

Item Type: Article
Keywords: Adenosine Triphosphatases/*metabolism Adenosine Triphosphate/metabolism Cell Cycle Proteins/*metabolism Chaperonins Circular Dichroism *Drosophila Proteins HSP90 Heat-Shock Proteins/*metabolism Humans Molecular Chaperones/*metabolism Spectrophotometry, Ultraviolet
Schools and Departments: School of Life Sciences > Biochemistry
Subjects: Q Science > QD Chemistry > QD0241 Organic chemistry > QD0415 Biochemistry
Depositing User: Chrisostomos Prodromou
Date Deposited: 24 Feb 2015 15:50
Last Modified: 24 Feb 2015 15:50
URI: http://sro.sussex.ac.uk/id/eprint/44380
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